The proposed research is designed to study the behavioral pharmacology of cocaine in humans, characterizing its effects on measures of learning and performance as well as its subjective effects. We plan to study the interaction of cocaine with alcohol and marijuana using a battery of learning, performance and subjective measures. We are particularly interested in evaluating the toxicity of cocaine when it is taken repeatedly for several days at a time, a pattern common to the illicit cocaine abuser. In addition to evaluating its effects during drug taking, we will evaluate a possible "crash" effect when drug taking stops, and its role as a potential setting condition in the reinitiation of cocaine use. We will also investigate the neurochemical mechanisms of cocaine's reinforcing properties, utilizing a drug choice paradigm and pretreating with various monoamine blockers. Finally, we will examine cocaine's reinforcing properties as they interact with its effects on other reinforcers in the environment. Thus, in evaluating cocaine's effects on behavior we will try to separate out its motoric and reinforcing effects on performance, as well as delineating the extent to which these effects contribute to enhanced reinforcing effectiveness of other reinforcers.